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Driver mutations lung cancer

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https://www.readbyqxmd.com/read/28647671/use-of-oncogenic-driver-mutations-in-staging-of-multiple-primary-lung-carcinomas-a-single-center-experience
#1
Ramsey Asmar, Joshua R Sonett, Gopal Singh, Mahesh M Mansukhani, Alain C Borczuk
PURPOSE: The staging of multiple pulmonary adenocarcinomas requires the distinction of intrapulmonary metastasis (IPM) from multiple primary lung cancers (MPLC). This can be challenging in some patients, and the addition of data from oncogenic driver mutations in these tumors may be helpful in this determination. PROCEDURES: As a proof of principle, molecular driver results from primary tumors and their metastases in 45 patients were compared (cohort 1). Then, 69 patients with a total of 154 synchronous or metachronous lung carcinomas were identified, with pathologic findings compared to oncogenic driver mutation...
June 21, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28637487/the-nf1-somatic-mutational-landscape-in-sporadic-human-cancers
#2
REVIEW
Charlotte Philpott, Hannah Tovell, Ian M Frayling, David N Cooper, Meena Upadhyaya
BACKGROUND: Neurofibromatosis type 1 (NF1: Online Mendelian Inheritance in Man (OMIM) #162200) is an autosomal dominantly inherited tumour predisposition syndrome. Heritable constitutional mutations in the NF1 gene result in dysregulation of the RAS/MAPK pathway and are causative of NF1. The major known function of the NF1 gene product neurofibromin is to downregulate RAS. NF1 exhibits variable clinical expression and is characterized by benign cutaneous lesions including neurofibromas and café-au-lait macules, as well as a predisposition to various types of malignancy, such as breast cancer and leukaemia...
June 21, 2017: Human Genomics
https://www.readbyqxmd.com/read/28636540/implementation-and-utilization-of-the-molecular-tumor-board-to-guide-precision-medicine
#3
REVIEW
Shuko Harada, Rebecca Arend, Qian Dai, Jessica A Levesque, Thomas S Winokur, Rongjun Guo, Martin J Heslin, Lisle Nabell, L Burt Nabors, Nita A Limdi, Kevin A Roth, Edward E Partridge, Gene P Siegal, Eddy S Yang
BACKGROUND: With rapid advances in genomic medicine, the complexity of delivering precision medicine to oncology patients across a university health system demanded the creation of a Molecular Tumor Board (MTB) for patient selection and assessment of treatment options. The objective of this report is to analyze our progress to date and discuss the importance of the MTB in the implementation of personalized medicine. MATERIALS AND METHODS: Patients were reviewed in the MTB for appropriateness for comprehensive next generation sequencing (NGS) cancer gene set testing based on set criteria that were in place...
June 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28633480/a-prospective-examination-of-circulating-tumor-cell-profiles-in-non-small-cell-lung-cancer-molecular-subgroups
#4
C R Lindsay, V Faugeroux, S Michiels, E Pailler, F Facchinetti, D Ou, M V Bluthgen, C Pannet, M Ngo-Camus, G Bescher, C Caramella, F Billiot, J Remon, D Planchard, J-C Soria, B Besse, F Farace
Background: We report the first study examining the clinical, numerical and biological properties of circulating tumor cells (CTCs) according to molecular subtypes of non-small cell lung cancer (NSCLC). Patients and Methods: 125 patients with treatment-naïve stage IIIb-IV NSCLC were prospectively recruited for CellSearch analysis. Anti-vimentin antibody was included for examination of CTCs to assess their mesenchymal character. Associations of total CTCs and vimentin-positive (vim +) CTCs with clinical characteristics, tumor genotype and survival were assessed...
June 19, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28611011/application-of-plasma-genotyping-technologies-in-non-small-cell-lung-cancer-a-practical-review
#5
REVIEW
Adrian G Sacher, Kimberly M Komatsubara, Geoffrey R Oxnard
The rational treatment of metastatic NSCLC hinges upon the timely detection of potentially targetable genomic alterations in order to guide therapy. Recent advances in highly sensitive genotyping technologies have allowed for the development of novel plasma genotyping assays which are capable of noninvasively detecting targetable alterations in plasma cell-free DNA without reliance on traditional tissue genotyping. The rapid development of plasma genotyping has led to an explosion in the number of assay platforms available from both commercial and laboratory sources...
June 10, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28606923/detection-of-driver-and-resistance-mutations-in-leptomeningeal-metastases-of-nsclc-by-next-generation-sequencing-of-cerebrospinal-fluid-circulating-tumor-cells
#6
Ben-Yuan Jiang, Yang-Si Li, Wei-Bang Guo, Xu-Chao Zhang, Zhihong Chen, Jian Su, Wenzhao Zhong, Xue-Ning Yang, Jinji Yang, Yang W Shao, Biao Huang, Yan-Hui Liu, Qing Zhou, Hai-Yan Tu, Hua-Jun Chen, Zhen Wang, Chongrui Xu, Bin-Chao Wang, Shu-Yu Wu, Cun-Yi Gao, Xian Zhang, Yi-Long Wu
<p>Leptomeningeal metastases (LM) are more common in non-small cell lung cancer (NSCLC) with EGFR mutations. The diagnosis is difficult by traditional imaging only, and leads to poor understanding of resistance mechanisms of LM.</p> <br />Experimental Design: <p>We compared the CellSearch Assay™, the Thinprep cytologic test (TCT), and brain magnetic resonance imaging (MRI) in 21 NSCLC patients with suspected LM. Next-Generation sequencing that included 416 cancer-associated genes was also performed on cerebrospinal fluid circulating tumor cells (CSFCTCs) of 19 patients...
June 12, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28584183/nature-and-nurture-what-determines-tumor-metabolic-phenotypes
#7
REVIEW
Jared R Mayers, Matthew G Vander Heiden
Understanding the genetic basis of cancer has led to therapies that target driver mutations and has helped match patients with more personalized drugs. Oncogenic mutations influence tumor metabolism, but other tumor characteristics can also contribute to their metabolic phenotypes. Comparison of isogenic lung and pancreas tumor models suggests that use of some metabolic pathways is defined by lineage rather than by driver mutation. Lung tumors catabolize circulating branched chain amino acids (BCAA) to extract nitrogen for nonessential amino acid and nucleotide synthesis, whereas pancreatic cancer obtains amino acids from catabolism of extracellular protein...
June 5, 2017: Cancer Research
https://www.readbyqxmd.com/read/28577945/systematic-identification-of-cancer-related-long-noncoding-rnas-and-aberrant-alternative-splicing-of-quintuple-negative-lung-adenocarcinoma-through-rna-seq
#8
Lu Zhang, Shiyong Li, Yoon-La Choi, Jinseon Lee, Zhuolin Gong, Xiaoqiao Liu, Yunfei Pei, Awei Jiang, Mingzhi Ye, Mao Mao, Xuegong Zhang, Jhingook Kim, Ronghua Chen
OBJECTIVES: Lung adenocarcinoma (LUAD) is a common subtype of non-small cell lung cancer prevalent in Asia. There is a dearth of understanding regarding the transcriptome landscape of LUAD without primary known driver mutations. In this study, LUAD samples without well-known driver mutations occurring in EGFR, KRAS, ALK, ROS1 or RET (quintuple-negative) were used for transcriptome study with a focus on long noncoding RNAs (lncRNAs), alternative splicing and gene fusions. MATERIALS AND METHODS: 24 pairs of LUAD and adjacent normal samples and 13 tumor-only samples derived from 37 quintuple-negative patients were used...
July 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28574849/strategies-targeting-angiogenesis-in-advanced-non-small-cell-lung-cancer
#9
REVIEW
Jun Wang, Jianpeng Chen, Yan Guo, Baocheng Wang, Huili Chu
Tumor angiogenesis is a frequent event in the development and progression of non-small cell lung cancer (NSCLC) and has been identified as a promising therapeutic target. The vascular endothelial growth factor (VEGF) family and other angiogenic factors, including fibroblast growth factor and platelet-derived growth factor, promote the growth of newly formed vessels from preexisting vessels and change the tumor microenvironment. To date, two antiangiogenic monoclonal antibodies, bevacizumab and ramucirumab, which target VEGF-A and its receptor VEGF receptor-2, respectively, have been approved for the treatment of locally advanced or metastatic NSCLC when added to first-line standard chemotherapy...
May 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28572536/the-detection-and-significance-of-egfr-and-braf-in-cell-free-dna-of-peripheral-blood-in-nsclc
#10
Yang Yang, Xiaoyan Shen, Rutian Li, Jie Shen, Hang Zhang, Lixia Yu, Baorui Liu, Lifeng Wang
OBJECTIVE: Although driver mutation status is crucial to targeted therapy decision-making in non-small cell lung cancer (NSCLC), due to unavailable or inadequate biopsies, there are still many patients with unknown mutation status. A promising way to solve this problem is liquid biopsy, such as cell-free DNA (cfDNA) in peripheral blood. Additionally, due to the little amount of cfDNA, detecting methods with high sensitivity, specificity and economy are required in clinical practice. Here, we explored the feasibility of Competitive Allele-Specific TaqMan® PCR (CastPCR) detecting driver mutations in cfDNA from plasma in lung adenocarcinoma patients...
May 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28566436/reactivation-of-the-p90rsk-cdc25c-pathway-leads-to-bypass-of-the-ganetespib-induced-g2-m-arrest-and-mediates-acquired-resistance-to-ganetespib-in-kras-mutant-nsclc
#11
Suman Chatterjee, Eric H-B Huang, Ian Christie, Timothy F Burns
A subset of non-small cell lung cancers (NSCLC) are dependent upon oncogenic driver mutations including the most frequently observed driver mutant KRAS which is associated with a poor prognosis.   As direct RAS targeting in the clinic has been unsuccessful to date, use of Heat shock protein 90 (Hsp90) inhibitors appeared to be a promising therapy for KRAS mutant NSCLC, however limited clinical efficacy was observed due to rapid resistance. Furthermore, the combination of the Hsp90 inhibitor (Hsp90i), ganetespib and docetaxel was tested in a phase III clinical trial and failed to demonstrate benefit...
May 31, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28559820/nivolumab-therapy-for-synchronous-alk-positive-lung-cancer-and-gastric-cancer
#12
Masahiro Yamasaki, Naomi Saito, Yu Hada, Sayaka Miyamoto, Hideharu Okanobu, Naoya Ikeda, Wakako Daido, Sayaka Ishiyama, Naoko Deguchi, Masaya Taniwaki, Nobuyuki Ohashi
Nivolumab is an immune checkpoint inhibitor with demonstrated efficacy against several malignant tumors. Alterations in driver oncogenes such as EGFR and ALK are a poor prognostic factor in nivolumab therapy for non-small cell lung cancer (NSCLC), whereas a smoking history is a well-known, favorable prognostic factor. However, an efficacy of nivolumab therapy for multiple primary malignant tumors (MPMTs) has not been reported, and its efficacy for driver oncogene-positive NSCLC in smokers is unclear. Herein, we report the case of a patient with a history of heavy smoking who developed synchronous ALK-positive NSCLC and gastric cancer that responded to nivolumab therapy...
January 2017: Case Reports in Oncology
https://www.readbyqxmd.com/read/28558851/-new-biopsy-at-lung-cancer-progression-rational-treatment-of-resistant-lung-cancer
#13
L B M Hijmering-Kappelle, A J van der Wekken, T J N Hiltermann, H J M Groen
Nowadays, patients with advanced non-small cell lung cancer harbouring a driver mutation undergo targeted treatment. This results in profound tumour responses but inevitably induces resistance after approximately 9 to 12 months. In this article we consider the importance and clinical implications of taking new biopsies to retrieve information regarding resistance mechanisms. There is a shift in the use of other modalities such as radiotherapy and surgery in patients with oligometastatic disease, producing long-lasting responses...
2017: Nederlands Tijdschrift Voor Geneeskunde
https://www.readbyqxmd.com/read/28555282/smarca4-deficient-pulmonary-adenocarcinoma-clinicopathological-immunohistochemical-and-molecular-characteristics-of-a-novel-aggressive-neoplasm-with-a-consistent-ttf1-neg-ck7-pos-heppar-1-pos-immunophenotype
#14
Abbas Agaimy, Florian Fuchs, Evgeny A Moskalev, Horia Sirbu, Arndt Hartmann, Florian Haller
Alterations in SMARCA4, a member of the chromatin remodeling Switch Sucrose Non-Fermentable (SWI/SNF) complex, characterize a subset of non-small cell lung cancer (NSCLC), but detailed morphological and immunophenotypic description of this tumor type is lacking. We describe 20 NSCLC cases found on routine screening not to express SMARCA4 by immunohistochemistry (IHC). These tumors were stained for CK7, TTF1, SMARCA2, SMARCA4, SMARCB1, and HepPar-1 and analyzed for molecular alterations, using a 160 cancer-related gene panel including the full coding sequence of SMARCA4...
May 30, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28554329/back-to-the-bench-mek-and-erk-inhibitors-for-the-treatment-of-kras-mutant-lung-adenocarcinoma
#15
Jens Köhler, Marco Catalano, Chiara Ambrogio
Lung cancer accounts for one in five cancer deaths worldwide. Mutations in the gene encoding for the Kirsten rat sarcoma (KRAS) oncoprotein define the largest molecular subset of non-small cell lung cancer (NSCLC) which is characterized by activated MAPK signaling. Unlike for other driver oncogenic events, such as EGFR and EML4-ALK aberrations, no targeted inhibitor of mutant KRAS or of downstream signaling molecules has yet been approved for routine clinical use. Downstream pathway inhibition with MEK and ERK inhibitors has some efficacy in pre-clinical models of KRAS mutant lung cancer, however, the clinical benefit for affected patients is limited due to dynamic kinome reprogramming and the lack of reliable predictive factors...
May 29, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28550959/coexistence-of-egfr-kras-braf-and-pik3ca-mutations-and-alk-rearrangement-in-a%C3%A2-comprehensive-cohort-of-326-consecutive-spanish-nonsquamous-nsclc-patients
#16
Paloma Martín Martorell, Marisol Huerta, Amparo Compañ Quilis, Rosario Abellán, Enrique Seda, Sebastián Blesa, Felipe J Chaves, Diego Dualde Beltrán, Susana Roselló Keränen, José Franco, Amelia Insa
INTRODUCTION: Molecular screening is crucial for the care of nonsquamous non-small-cell lung cancer (NSCLC) patients. The coexistence of mutations could have important consequences regarding treatment. We described the mutational patterns and coexistence among patients and their outcomes after targeted treatment. MATERIALS AND METHODS: Data from consecutive patients with newly diagnosed nonsquamous NSCLC were prospectively collected. Next-generation sequencing analysis of mutational hotspots in the EGFR, KRAS, PIK3CA, and BRAF genes and analysis of anaplastic lymphoma kinase (ALK) rearrangement were performed...
April 27, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28546520/-omic-approach-in-non-smoker-female-with-lung-squamous-cell-carcinoma-pinpoints-to-germline-susceptibility-and-personalized-medicine
#17
Margherita Baldassarri, Chiara Fallerini, Francesco Cetta, Marco Ghisalberti, Cristiana Bellan, Simone Furini, Ottavia Spiga, Sergio Crispino, Giuseppe Gotti, Francesca Ariani, Piero Paladini, Alessandra Renieri, Elisa Frullanti
Purpose: Lung cancer is strongly associated to tobacco smoking. However, global statistics estimate that in females the proportion of lung cancer cases that is unrelated to tobacco smoking reaches fifty percent, making questionable the etiology of the disease. Materials and Methods: A never-smoker female with primary EGFR/KRAS/ALK-negative squamous cell carcinoma of the lung and their normal sibs were subjected to a novel integrative "omic" approach using a pedigree-based model for discovering genetic factors leading to cancer in the absence of well-known environmental trigger...
May 26, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/28544061/survival-difference-according-to-mutation-status-in-a-prospective-cohort-study-of-australian-patients-with-metastatic-non-small-cell-lung-carcinoma-nsclc
#18
Lavinia Tan, Marliese Alexander, Ann Officer, Michael MacManus, Linda Mileshkin, Ross Jennens, Dishan Herath, Richard de Boer, Stephen B Fox, David Ball, Benjamin Solomon
BACKGROUND AND OBJECTIVE: Non-small cell lung cancer (NSCLC) is a heterogeneous disease comprising not only different histologic subtypes but also different molecular subtypes. Our objective is to describe the frequency of oncogenic drivers in patients with metastatic NSCLC, the proportion of patients tested and survival difference according to mutation status in a single-institution study. METHODS: Metastatic NSCLC patients enrolled onto a prospective Thoracic Malignancies Cohort (TMC) Study between July 2012 and August 2016 were selected...
May 24, 2017: Internal Medicine Journal
https://www.readbyqxmd.com/read/28535939/gene-expression-profiling-of-large-cell-lung-cancer-links-transcriptional-phenotypes-to-the-new-histological-who2015-classification
#19
Anna Karlsson, Hans Brunnström, Patrick Micke, Srinivas Veerla, Johanna Mattsson, Linnea La Fleur, Johan Botling, Mats Jönsson, Christel Reuterswärd, Maria Planck, Johan Staaf
INTRODUCTION: Large cell carcinoma with or without neuroendocrine features (LCNEC and LC, respectively) constitutes a small proportion of non-small cell lung cancer (NSCLC). The WHO2015 classification guidelines changed the definition of the debated histological subtype LC to be based on immunomarkers for adenocarcinoma and squamous cancer. We sought to determine if these new guidelines translate also to the transcriptional landscape of lung cancer, and LC specifically. METHODS: Gene expression profiling was performed using Illumina V4 HT12 microarrays on 159 cases (comprising all histological subtypes including 10 WHO2015 LC and 14 LCNEC tumors), with complimentary mutational and IHC data...
May 20, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28532538/-aberrant-expression-of-rb-and-prb-780-prb-795-in-lung-adenocarcinoma-patients-with-egfr-mutations-and-their-clinical-significance
#20
Yunlong Dong, Minghui Liu, Yongwen Li, Ying Li, Chenlong Zhao, Yin Yuan, Hui Du, Zihe Zhang, Hongbing Zhang, Hongyu Liu, Jun Chen
BACKGROUND: Rb is an important tumor suppressor gene that regulates cell cycle progression. Rb dysfunction can lead to over proliferation of cells and lead to the occurrence of tumor. Loss or reduced Rb expression as well as over phosphorylation of Rb are important mechanisms of Rb dysfunction. The mutated epidermal growth factor receptor (EGFR) gene is an important driver gene in lung adenocarcinoma, and plays an important role in the development of lung cancer. The purpose of this study was to investigate the status of Rb in lung adenocarcinoma patients with EGFR mutations and define the clinicopathologic features...
May 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
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